Coagulation
Hereditary bleeding disorders
Factor XI deficiency
Last author update: 1 October 2010
Last staff update: 21 September 2020
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PubMed Search: Factor XI deficiency [title]
Table of Contents
Definition / general | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Laboratory | Case reports | Treatment | Differential diagnosis | Additional referencesCite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Factor XI deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationfactorXIdef.html. Accessed April 19th, 2024.
Definition / general
- Factor XI deficiency is a rare bleeding disorder that is inherited most commonly as an autosomal recessive trait, and is characterized by variable bleeding episodes
Sites
- Bleeding into skin and mucosa, genitourinary tract, gastrointestinal tract (see clinical features below)
Pathophysiology
- Factor XI is a serine protease that is produced in the liver, and is involved in the contact (intrinsic) pathway
- It is activated by factor XIIa, thrombin or autoactivated, and activates factor IX, which in turn activates factor X to convert prothrombin to thrombin
- Its biologic half-life is 60 - 80 hrs
Etiology
- Most commonly inherited as an autosomal recessive trait
- An autosomal dominant pattern of inheritance is possible, as the dimeric structure of factor XI may result in a dominant negative effect through intracellular heterodimer formation (Blood 2004;104:128)
- The gene for factor XI is located on the long arm of chromosome 4
- To date, over 180 mutations have been described with three main genotypes: type I are splice site mutations, type II are nonsense mutations and type III are missense mutations
- Type II and III mutations are predominantly seen in Ashkenazi Jews
- Type II mutations are also seen in Iraqi Jews and Israeli Arabs
Diagrams / tables
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Coagulation cascade
Clinical features
- Deficiency can occur in homozygous, heterozygous or a combined heterozygous form
- Bleeding manifestations do not correlate with factor XI levels
- Most bleeding episodes in patients with severe deficiency are injury-related
- Spontaneous bleeding is rare
- May be associated with bruising, epistaxis, menorrhagia, GI / GU bleeding, umbilical stump bleeding or bleeding after surgery, trauma, dental procedures, pregnancy or circumcision
- Up to 33% of patients with severe deficiency develop inhibitors after replacement therapy
Laboratory
- Prolonged PTT that corrects with mixing study
- Normal PT, thrombin time
- Specific factor XI assay
Case reports
- Cerebellar hemorrhage due to factor XI deficiency (Cerebrovasc Dis 2005;19:138)
Treatment
- 10 - 20 ml fresh frozen plasma/kg, then 5 - 10 ml/kg every 24 hours as necessary
- Antifibrinolytic therapy has been used in women with factor XI deficiency and menorrhagia
- Patients with inhibitors have been treated successfully with plasma, prothrombin complex concentrates, and recombinant activated factor VII
- Note: factor XI concentrates may promote thromboembolic complications
Differential diagnosis
- Acquired factor XI deficiency associated with systemic lupus erythematous
- Combined familial factor deficiency
- Heparin contamination
- Liver dysfunction
- Other factor deficiency causing prolonged PTT: factor VIII, IX, XII, but factor XII deficiency is not associated with bleeding manifestations
- von Willebrand Disease
Additional references
